Multiple-Dose Arecoline Infusions in Alzheimer's Disease

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Abstract
• Twelve patients with dementia of the Alzheimer type received two-hour infusions of placebo and the muscarinic cholinergic agonist arecoline hydrobromide at rates of 1,2, and 4 mg/h in a double-blind, randomized fashion. These infusions resulted in dose-dependent physiologic and neuroendocrine effects consistent with central cholinergic stimulation. Infusions were generally well tolerated. No statistically significant improvement in performance on most cognitive tasks assessing knowledge memory and episodic learning and memory was observed at any dose, although marginal improvement in picture recognition ability and in ratings of word-finding were observed at the lower doses. Psychomotor activation and slightly improved affect were reliably observed at the lower doses, whereas increasing psychomotor retardation was observed at the highest dose. The data support a role for central cholinergic modulation of some aspects of cognition, behavior, and affect in this population. The apparent greater behavioral sensitivity of patients with Alzheimer's disease in comparison with subject populations previously studied, as well as the altered dose responsiveness, merit further study in relationship to normal aging.